| dc.description.abstract | Immunoterapiaren helburua da gaixoen immunitate-sistema indartuz minbizia bezalako gaitz larriak menderatzea. Horretarako, gaixoak maiz 2-interleukina (IL-2) deitzen den konposatu batekin tratatzen dira, izan ere molekula honek berebi-ziko ahalmena baitauka T-zelulen edo T linfozitoen hazkuntza sustatzeko. Zoritxarrez, IL-2ren erabilerak albo kalte desatseginak eragiten ditu gaixoetan, eta hauek ekiditeko ezinbestekoa da IL-2k T-zeluletan eragiten dituen molekula mailako aldaketak sakon aztertu eta ulertzea. Zelulen gainazalera heltzen diren seinaleak zelulan barrena ga-rraiatzen dira nagusiki proteinen behin behineko fosforilazioen bidez. Hori horrela, au-rreko lan batean, IL-2k T linfozitoetan pizten dituen seinalizazio-bidezidorrak aztertu genituen zelulen zitoplasman fosforilatzen diren proteinak masa espektrometriaren bi-dez identifikatuz. Oraingo lan honetan berriz, masa espektrometriaren laguntzaz aztertu da IL-2k nola erregulatzen duen T-zelulen nukleoko proteinen fosforilazio maila, izan ere horrek zuzenean eragingo baitu geneen erregulazioan eta horrenbestez baita zelu-laren patuan ere. Esperimentu bera 3 aldiz errepikatu ostean, gutxienez behin identifi-katu eta kuantifikatu dira lan honetan T-zelulen nukleoko proteinetan fosforilatutako 8.521 aminoazido, horietako haietako asko aurrez ezagutugabeak. Bestalde, ikusi da orkorrean berdinantzera mantentzen dela IL-2rekin tratatutako eta tratatu gabeko T-ze-luletako fosforilazio maila. Halere, azpimarragarria da IL-2ren ondorioz 391 aminoa-zidoren fosforilazio maila nabarmen aldatzen dela T-zelulen nukleoetan. Etorkizunean egingo diren ikerkuntzek argituko dute zein den IL-2ren menpeko fosforilazio hauen esanahi biologikoa.; Immunotherapy aims to fight against diseases such as cancer by boosting the immune system of the patients. For that purpose, patients are usually treated with a molecule called interleukin-2 (IL-2), which plays a pivotal role in modulating the im-mune system and specially in promoting the proliferation of T-cells. Unfortunately, ad-ministration of IL-2 is usually accompanied by severe side effects that must be over-come. To achieve this, it is mandatory to understand in detail the molecular effects triggered in T-cells upon IL-2 stimulation. It is known that signaling events initiated at the cell surface are mainly transduced inside the cell through transient phosphoryla-tions occurring in distinct proteins. For that reason our previous study focused on dis-secting the signaling pathways triggered in IL-2-treated T lymphocytes by studying the proteins that become tyrosine phosphorylation upon the stimuli using mass spectrome-try. In the present study, we aimed to unveil how IL-2 modulates the phosphorylation status of the nuclear proteins in T-cells, which ultimately will affect gene expression and the fate of the cell. Following a quantitative mass spectrometry-based approach a total of 8,521 phosphorylated aminoacids were quantified at least in one of the 3 repli-cas of the same experiment that were performed. Whereas the phosphorylation levels of most phosphosites remained unaffected in IL-2-treated and untreated T-cells, the phosphorylation status of 391 phosphosites was found to be dramatically modulated upon IL-2 stimulation. Further investigation will unveil the biological significance of such findings | |
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